Therapeutic formulations containing venom or venom anti-serum either alone or in combination for the therapeutic prophylaxis and therapy of neoplasms

Abstract

The present invention comprises the method of treating host organisms (i.e. human or animal) in need of a drug having anti-neoplastic activity comprising the administration of a therapeutically effective amount of venom anti-serum either alone or preferably in combination with a Phospholipase C inhibitor of non-toxic nature or monoclonal or polyclonal anti-serum to Phospholipase C enzyme or a vaccine containing in whole or in part venom and/or other components of animal, insect or plant origin showing Phosphiolipase A 2 and/or Phospholipase C activity. This patent presents pharmaceutical formulations containing snake and/or insect venoms, or extracts from such venoms which may contain, total or partial, Phospholipase A 2 enzyme activity alone or in combination with animal or plant Phospholipase A 2 with or without Phospholipase C inhibiting compounds or Phospholipase C mono- or polyclonal anti-serum to Phospholipase C enzyme as Phospholipase C mono- or polyclonal anti-serum to Phospholipase C enzyme as therapeutic vaccine candidate for all neoplastic diseases. This patent presents therapeutic pharmaceutical formulations containing anti-serum to snake and/or insect venoms wherein the anti-serum is preferably affinity purified for use in treating neoplastic diseases. This patent presents pharmaceutical formulations containing organic polymer mimic molecules generated to snake and/or insect and/or mammalian and/or plant PLA 2 enzymes or epitopes, or extract from such venoms or synthetic peptides and/or other molecules which may contain, total or partial, Phospholipase A 2 and C enzyme activity.

I claim  
     
         1 . A method of treating neoplasm in a mammal in need of such treatment, comprising administering to said mammal a therapeutic agent comprising venom and/or mammalian. plant or insect anti-serum reactive with at least one Phospholipase A 2  enzyme.  
     
     
         2 . A method according to  claim 1  wherein the anti-serum is reactive with two or more Phospholipase A 2  type enzymes.  
     
     
         3 . A method according to  claim 1  wherein the at least one Phospholipase A 2  Type enzyme is Type I, Type II, Type III or Type IV.  
     
     
         4 . A method according to  claim 1  wherein the anti-serum is either polyclonal or monoclonal.  
     
     
         5 . A method of treating a mammal prophylactically to prevent neoplastic development, comprising administering to said mammal a therapeutic vaccine containing venom and/or mammalian, plant or insect PLA 2  enzymes or part thereof as the principal antigen component.  
     
     
         6 . A pharmaceutical formulation containing venom and/or mammalian plant or insect anti-serum to PLA 2  enzyme or part thereof in combination with anti-serum to Phospholipase C enzyme or part thereof or inhibitory compounds to Phospholipase C for use as a therapeutic agent for the therapy of a neoplastic condition in a human or animal.  
     
     
         7 . A method according to  claim 6  wherein the inhibitory compounds to Phospholipase C is one or more of EDTA, Phenanthroline, Chloromercuribenzoic Acid, lodoacetic Acid, and I-oleoyl-2-acetyl-sn-glycerol(OAG).  
     
     
         8 . A pharmaceutical formulation containing one or more venoms or venom components as antigen and/or mammalian, plant or insect PLA 2  enzyme as antigen in combination with Phospholipase C enzyme.  
     
     
         9 . A method according to  claim 8  wherein the phospholipase C enzyme inhibitor is used in combination with the therapeutic agents of claim I to enhance anti neoplastic and anti metastatic activity.  
     
     
         10 . A method according to any one of claims  1 ,  5 ,  6  and  8 , wherein the administration is part of a combination therapy with other therapeutically effective agents.  
     
     
         11 . A method according to claims  1 ,  5 ,  6  and  8  wherein the administration is in combination with adjuvants.  
     
     
         12 . A method according to claims  1 ,  5 ,  6  and  8  wherein the venom is that of snakeand/or insect.  
     
     
         13 . A method according to claims  1 ,  5 ,  6  and  8  wherein the Phospholipase A 2  enzyme showing Phospholipase A 2  activity is obtained from more than one species of snake and/or insect, mammal or plant.  
     
     
         14 . A method according to claims  1 ,  5 ,  6  and  8  wherein the therapeutic agent is administered as an anti-inflammatory agent.  
     
     
         15 . A method according to claims  1 ,  5 ,  6  and  8  wherein the therapeutic agent is administered to prevent the occurrence of immunosuppression.  
     
     
         16 . A method according to claims  1 ,  5 ,  6  and  8  wherein the therapeutic agent is administered in the treating of allergic contact dermatitis, Asthma and Psoriasis and bronchitis.  
     
     
         17 . A method according to claims  1 ,  5 ,  6  and  8  wherein the anti-serum is administered for the treatment of physiological condition resultant from elevated levels of phospholipase A 2  products and/or metabolites.  
     
     
         18 . A method according to  claim 17  wherein the physiological condition is Schizophrenia.  
     
     
         19 . A method according to claims  1 ,  5 ,  6 ,  8  and  17  wherein the anti-serum to Phospholipase A 2  and/or C are produced synthetically by molecular imprinting of template organic molecules using these enzymes.  
     
     
         20 . Therapeutic agents according to claims  1 ,  5 ,  6  and  8  for treating one or more of the following:- Rheumatoid arthritis, osteoarthritis, gout, rheumatic carditis and autoimmune diseases, allergic diseases, bronchial asthma, septic shock, renal failure, pancreatis, myasthenia gravis and ocular and dermal inflammatory diseases, psoriasis, splenomegaly, cancer, metastatic spread of neoplasm, collagen vascular disease, myocardial ischemia, cellular chemotaxis, depression, erythema, vascular permeability resultant from enhanced production of PGE 2 , acne, atopic diseases, malaria, allergic conjunctivitis, schizophrenia, reiters syndrome, raynaud's phenomenon, lupus, Chron's and Graves disease.  
     
     
         21 . A method according to claims  1 ,  5 ,  6 ,  8  and  17  wherein the Fc receptor of the antibody to either Phospholipase A 2  and C used in this therapeutic method is either totally or partially removed.  
     
     
         22 . A method according to claims  6 ,  8 ,  19  and  21  wherein a non-toxic compound demonstrating inhibiting activity against Phospholipase C enzymes may be utilised in conjunction with the PLA 2  anti-serum to enhance its anti-neoplastic (tumour) and anti-metastatic activity.  
     
     
         23 . A method according to claims  1 ,  5 ,  6 ,  8 , 17  and  19  wherein the anti-serum is generated to human Phospholipase A 2  enzyme either in a mono and/or polyclonal form.  
     
     
         24 . A method according to claims  1 ,  5 ,  6 ,  8  and  17  wherein the anti-serum to Phospholipase A 2  enzyme is generated in eggs, producing antibodies which do not react with the human Compliment system.  
     
     
         25 . A method according to claims  1 ,  5 ,  6 ,  8  and  17  wherein the anti-serum to venom, mammalian, plant or insect Phospholipase A 2  is generated in mammals and extracted from the colostrum and preferably but not essentially affinity purified for use in oral administration to patients either alone or in combination with anti-serum similarly produced to human Phospholipase C enzyme components.  
     
     
         26 . A method of inoculation of human or animal with a combination of two or more phospholipase A 2  enzymes types.  
     
     
         27 . A method according to  claim 26  where the antibody response to the inoculation confers prophylactic and/or therapeutic benefit to patient.  
     
     
         28 . A method according to  claim 27  wherein the patient is in need of a treatment for a neoplastic condition.  
     
     
         29 . A method according to claims  26 ,  27  and  28  wherein the phospholipase A 2  type is Type I, Type II, Type III or Type IV.  
     
     
         30 . A method according to  claim 29  wherein the Phospholipase A 2  is obtained from venom.  
     
     
         31 . A method according to  claim 29  wherein the Phospholipase A 2  is obtained from animal or plant species.  
     
     
         32 . A method according to  claim 1 ,  5 ,  6 ,  8  and  26  wherein the phospholipase A 2  is synthetically produced or cloned.  
     
     
         33 . A method of early detection of neoplastic disease by utilising the detection of enhanced PLA 2  levels in patients.  
     
     
         34 . A method according to  claim 33  wherein the detection of enhanced PLA 2  is established by the use of Lipose Diagnostic Kit.  
     
     
         35 . A method according to claims  2 ,  26 ,  27  and  28  wherein Phospholipase A 2  type enzyme has a size of between 40-80 kDa.  
     
     
         36 . A method of targeting cancer cells by use of Type I and/or Type II PLA 2  as targeting agent with hydrophilic tail.  
     
     
         37 . A method according to  claim 36  wherein the targeting agent is a liposome containing anti-serum to PLA 2  or conventional chemotherapy drugs.  
     
     
         38 . A method treating parasitic and bacterial infections in mammals by the administration of a therapeutic agent containing venom and/or mammalian, plant or insect anti-serum reactive with Phospholipase A 2  enzymes  
     
     
         39 . A method according to  claim 38  wherein the anti-serum is reactive with one or more Phospholipase A 2  type enzymes  
     
     
         40 . A method according to  claim 39  wherein the Phospholipase A 2  Type enzymes is one of Type I, Type II, Type III or Type IV.  
     
     
         41 . A method according to  claim 38  wherein said parasite is an haemoflagellate parasite.  
     
     
         42 . A method as recited in  claim 41  wherein said parasite is a member of the group of haemoflagellate parasites consisting of Leishmania, Trypanosomia and Toxoplasma.